Human peri-tumoral and lung fibroblasts produce paracrine motility factors for recently established human sarcoma cell strains.

Abstract:

:Paracrine motogenic cytokines secreted by normal cells can stimulate metastatic cell invasion. For example, human fibroblasts secrete hepatocyte growth factor/scatter factor (HGF/SF), which stimulates paracrine migration of epithelial and certain carcinoma cells, and migration-stimulating factor (MSF), which stimulates autocrine migration of fibroblasts from certain breast carcinomas. We found that human peri-tumoral and lung fibroblasts secrete motility-stimulating activity for several recently established human sarcoma cell strains. Motility of lung metastasis-derived SYN-I sarcoma cells was preferentially stimulated by human lung and peri-tumoral fibroblast motility-stimulating factors (FMSFs). FMSFs were non-dialyzable, susceptible to trypsin and sensitive to dithiothreitol. Cycloheximide inhibited accumulation of FMSF activity in conditioned medium; however, addition of cycloheximide to the migration assay did not significantly affect motility-stimulating activity. Purified HGF/SF, rabbit anti-hHGF and RT-PCR analysis of peri-tumoral and lung fibroblast HGF/SF mRNA expression indicated that FMSF activity was unrelated to HGF/SF. Partial purification of FMSF by gel exclusion chromatography revealed several peaks of activity, suggesting multiple FMSF molecules or complexes. Since human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), FMSF may play a role in this process independent of HGF/SF.

journal_name

Int J Cancer

authors

Hu M,Pollock RE,Nakamura T,Nicolson GL

doi

10.1002/ijc.2910620516

subject

Has Abstract

pub_date

1995-09-04 00:00:00

pages

585-92

issue

5

eissn

0020-7136

issn

1097-0215

journal_volume

62

pub_type

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